scholarly journals Establishing correlation of axial and vertical force of cardiac artificial tissue using a novel micromachined sensor

2020 ◽  
Author(s):  
Angelo Gaitas ◽  
Francesca Stillitano ◽  
Irene Turnbull
Keyword(s):  
Single Cell ◽  
Axial Force ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Heart Tissue ◽  
Vertical Force ◽  
Force Microscopy ◽  
Artificial Tissue ◽  
One Step ◽  
Engineered Tissue

AbstractCardiomyocytes iPSC (iPSC-CMs) have great potential for cell therapy, drug assessment, and for understanding the pathophysiology and genetic underpinnings of cardiac diseases. Contraction forces are one of the most important characteristics of cardiac function and are predictors of healthy and diseased states. Cantilever techniques, such as atomic force microscopy, measure the vertical force of a single cell, while systems designed to more closely resemble the physical heart function, such as cardiac tissue on posts, measure the axial force. One important question is how do these two force measurements correlate? By establishing a correlation of the axial and vertical force we will be one step closer in being able to use single cell iPSC instead of more elaborate human engineered tissue or animal heart tissue as models. A novel micromachined sensor for measuring force contractions of artificial tissue has been developed. Using this novel sensor a correlation between axial force and vertical force is experimentally established. This finding supports the use of vertical measurements as an alternative to tissue measurements.

scholarly journals Loss of the Long Non-coding RNA OIP5-AS1 Exacerbates Heart Failure in a Sex-Specific Manner

2021 ◽  
Author(s):  
Aowen Zhuang ◽  
Anna C. Calkin ◽  
Shannen Lau ◽  
Helen Kiriazis ◽  
Daniel G. Donner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Function ◽  
Cardiac Tissue ◽  
Cardiac Development ◽  
Heart Function ◽  
Pressure Overload ◽  
Enrichment Analysis ◽  
Heart Tissue ◽  
Gene Set Enrichment Analysis ◽  
Knock Out

AbstractBackgroundLong ncRNAs (lncRNAs) are known to influence numerous biological processes including cellular differentiation and tissue development. They are also implicated in the maintenance, health and physiological function of many tissues including the heart. Indeed, manipulating the expression of specific lncRNAs has been shown to improve pathological cardiac phenotypes such as heart failure. One lncRNA studied in various settings is OIP5-AS1 (also known as 1700020I14Rik and Cyrano), however its role in cardiac pathologies remains mostly uncharacterised.MethodsWe used data generated from FACS sorted murine cardiomyocytes, human iPSC derived cardiomyocytes, as well as heart tissue from various animal models to investigate OIP5-AS1 expression in health and disease. Using CRISPR we engineered a global OIP5-AS1 knock out (KO) mouse model and performed cardiac pressure overload experiments to study heart failure in these animals. RNA-sequencing of left ventricles provided mechanistic insight between WT and KO mice.ResultsWe demonstrate that OIP5-AS1 expression is regulated during cardiac development and cardiac specific pathologies in both rodent and human models. Moreover, we demonstrate that global female OIP5-AS1 KO mice develop exacerbated heart failure, but male mice do not. Transcriptomics and gene set enrichment analysis suggests that OIP5-AS1 may regulate pathways that impact mitochondrial function.ConclusionsOIP5-AS1 is regulated in cardiac tissue and its deletion leads to worsening heart function under pressure overload in female mice. This may be due to impairments in mitochondrial function, highlighting OIP5-AS1 as a gene of interest in sex-specific differences in heart failure.

scholarly journals Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties

2021 ◽  
Vol 22 (9) ◽  
pp. 5006
Author(s):  
Jelica Grujić-Milanović ◽  
Vesna Jaćević ◽  
Zoran Miloradović ◽  
Djurdjica Jovović ◽  
Ivica Milosavljević ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Morphological Changes ◽  
Chronic Administration ◽  
Heart Tissue ◽  
Severe Form ◽  
Malignant Hypertension ◽  
Experimental Hypertension ◽  
Resveratrol Treatment

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

scholarly journals Recapitulating Cardiac Structure and Function In Vitro from Simple to Complex Engineering

Micromachines ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 386
Author(s):  
Ana Santos ◽  
Yongjun Jang ◽  
Inwoo Son ◽  
Jongseong Kim ◽  
Yongdoo Park
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Computational Modeling ◽  
Cardiac Tissue ◽  
Cardiac Development ◽  
Heart Tissue ◽  
Cardiac Tissue Engineering ◽  
Cardiac Cells

Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, and regeneration. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication, and computational modeling to model the complexity of heart tissue. Here, we review the recent progress of engineering techniques from simple to complex for fabricating matured cardiac tissue in vitro. Advancements in cardiomyocytes, extracellular matrix, geometry, and computational modeling will be discussed based on a technology perspective and their use for preparation of functional cardiac tissue. Since the heart is a very complex system at multiscale levels, an understanding of each technique and their interactions would be highly beneficial to the development of a fully functional heart in cardiac tissue engineering.

Calibration of single-cell model parameters based on membrane resistance improves the accuracy of cardiac tissue simulations

2021 ◽  
pp. 101375
Author(s):  
Elnaz Pouranbarani ◽  
Lucas Arantes Berg ◽  
Rafael Sachetto Oliveira ◽  
Rodrigo Weber dos Santos ◽  
Anders Nygren
Keyword(s):  
Single Cell ◽  
Cardiac Tissue ◽  
Cell Model ◽  
Membrane Resistance ◽  
Model Parameters ◽  
Single Cell Model

Abstract 126: Peroxisomal Proliferator Activated Receptor Alpha Overexpression in Hypertrophied Cardiomyocytes Restores Mitochondrial Integrity and Function

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana
Keyword(s):  
Energy Demand ◽  
Cardiac Tissue ◽  
Structural Integrity ◽  
Heart Function ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Production ◽  
Receptor Alpha ◽  
And Function

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.

scholarly journals The effects of acutely and subchronically applied DL-methionine on plasma oxidative stress markers and activity of acetylcholinesterase in rat cardiac tissue

2020 ◽  
Vol 77 (2) ◽  
pp. 165-173
Author(s):  
Zarko Micovic ◽  
Sanja Kostic ◽  
Slavica Mutavdzin ◽  
Aleksa Andrejevic ◽  
Aleksandra Stamenkovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Ache Activity ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Antioxidant Defense System ◽  
Rat Plasma ◽  
Physiological Solution ◽  
Control Group ◽  
Subchronic Treatment

Background/Aim. Chronically induced hypermethioninemia leads to hyperhomocysteinemia which causes oxidative stress, atherogenesis, neurodegeneration and cancer. However, little is known about the acute and subchronic effects of DL-methionine (Met). The aim of study was to assess the effects of acutely and subchronically applied Met on oxidative stress parameters in rat plasma [enzymes: catalase (CAT), glutathione peroxidise (GPx), superoxide dismutase (SOD) and index of lipid peroxidation, malondialdehyde (MDA)], and acetylcholinesterase (AChE) activity in rat cardiac tissue. Methods. The enzymes activities, as well as MDA concentration were evaluated following acute (n = 8) and subchronic (n = 10) application of Met [i.p. 0.8 mmoL/kg body weight (b.w.) in a single dose in the acute overload or daily during three weeks in the subchronic overload]. The same was done in the control groups following application of physiological solution [i.p. 1 mL 0.9% NaCl (n = 8) in the acute overload and 0.1?0.2 mL 0.9% NaCl, daily during three weeks (n =10) in the subchronic overload]. Tested parameters were evaluated 60 minutes after application in acute experiments and after three weeks of treatment in subchronic experiments. Results. There were no difference in homocysteine values between the groups treated with Met for three weeks and the control group. Met administration significantly increased the activity of CAT and GPx after 1 h compared to the control group (p = 0.008 for both enzymes), whereas the activity of SOD and MDA concentrations were unchanged. Subchronically applied Met did not affect activity of antioxidant enzymes and MDA level. AChE activity did not show any change in rat cardiac tissue after 1 h, but it was significantly decreased after the subchronic treatment (p = 0.041). Conclusion. Results of present research indicate that Met differently affects estimated parameters during acute and subchronic application. In the acute treatment Met mobilizes the most part of antioxidant enzymes while during the subchronic treatment these changes seems to be lost. On the contrary, the acute Met overload was not sufficient to influence on the AChE activity, while longer duration of Met loading diminished function of the enzyme. These findings point out that methionine can interfere with antioxidant defense system and cholinergic control of the heart function.

scholarly journals PO-301 Study on the effects of bone marrow-derived stem cells were used in chronic hyperactivity rats to cardiac injury treatment

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Lei Xu ◽  
YiBo Niu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Test Data ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Training Group ◽  
Significant Difference ◽  
General Training

Objective  overload and long-term overtraining can cause hypoxic and hypoxic damage to the myocardial structure of the body. In recent years, studies have shown that the stem cells promote angiogenesis in vivo, resistance to apoptosis, myocardial stem cell mobilization, and promote its proliferation in paracrine effect, such as vascular distribution. By animal experiments, this study explore MSCMs role in the improvement of heart function and its molecular mechanism to sports injury prevention and postoperative rehabilitation is of great significance of the heart, heart research provides the basis for the motion at the same time support. Methods Wistar rat model of excessive swimming training. Grouping: rats were randomly divided into 4 groups (n=10), quiet feeding group (Q), general training group (ET), over-training group (OT), and MSCMs transplant-over-training group (MOT). Source and preparation of stem cells: the rat autologous bone marrow was extracted 1 day before surgery, and the bone marrow mononuclear cells were isolated by Ficoll density gradient centrifugation. Methods of stem cell transplantation: perfusion via coronary artery in MOT group rats; Test indicators and methods: cardiac tissue was taken after the end of 1d training (group Q, ET and OT), MEF2A factor was tested by rcal-time, gata-4 expression was tested by Western blot, and LVEF value was observed by cardiac color doppler ultrasound (before, after 1w, after 2w and after 3w, respectively). Results MEF2A factor, gata-4 expression and LVEF value of the three groups of samples were detected: (1) compared with MEF2A factor in general training group (ET) and quiet group (Q), gata-4 expression was slightly improved, but there was no significant difference (P>0.05). After 3w, the increase of LVEF value presented significant differences (Pwhile 1w and 2w showed no significant differences compared with the quiet group. (2) comparison between the over-training group (OT) and the quiet group (Q) showed significant differences in MEF2A factor, gata-4 expression, and LVEF decreased value (P0.05) between the two groups after 2w and the quiet group (Q). Cardiac tissue was taken after 2w to observe the expression of MEF2A, and gata-4 was compared with the silent group (Q) without significant difference (P>0.05). Conclusions (1) based on the test data of general training group (ET), reasonable and scientific aerobic exercise can effectively enhance the cardiac function and improve the cardiac activity ability. (2) according to the test data of over-training group (OT), overloading and long-term over-training can lead to hypoxia of heart function and decrease of vitality, resulting in hypoxia and ischemia of the motor heart and damage of cardiac function. (3) according to the observation and test data of the MSCMs transplant-over-training group (MOT), MSCMs transplantation can effectively improve the cardiac function of sports injuries, enhance the cardiac vitality, and repair damaged cells and tissues to a certain extent. It can effectively prevent and treat heart injury caused by overtraining. At the same time, it provides animal experimental research support for the research of sports heart in sports medicine.

scholarly journals A Transcriptional Switch Governing Fibroblast Plasticity Underlies Reversibility of Chronic Heart Disease

2020 ◽  
Author(s):  
Michael Alexanian ◽  
Pawel F. Przytycki ◽  
Rudi Micheletti ◽  
Arun Padmanabhan ◽  
Lin Ye ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cardiac Function ◽  
Single Cell ◽  
Cardiac Dysfunction ◽  
Cardiac Fibroblasts ◽  
Regulatory Elements ◽  
Heart Tissue ◽  
Chromatin Accessibility ◽  
Fibroblast Activation ◽  
Transcriptional Switch

AbstractIn diseased organs, stress-activated signaling cascades alter chromatin, triggering broad shifts in transcription and cell state that exacerbate pathology. Fibroblast activation is a common stress response that worsens lung, liver, kidney and heart disease, yet its mechanistic basis remains poorly understood1,2. Pharmacologic inhibition of the BET family of transcriptional coactivators alleviates cardiac dysfunction and associated fibrosis, providing a tool to mechanistically interrogate maladaptive fibroblast states and modulate their plasticity as a potential therapeutic approach3–8. Here, we leverage dynamic single cell transcriptomic and epigenomic interrogation of heart tissue with and without BET inhibition to reveal a reversible transcriptional switch underlying stress-induced fibroblast activation. Transcriptomes of resident cardiac fibroblasts demonstrated robust and rapid toggling between the quiescent fibroblast and activated myofibroblast state in a manner that directly correlated with BET inhibitor exposure and cardiac function. Correlation of single cell chromatin accessibility with cardiac function revealed a novel set of reversibly accessible DNA elements that correlated with disease severity. Among the most dynamic elements was an enhancer regulating the transcription factor MEOX1, which was specifically expressed in activated myofibroblasts, occupied putative regulatory elements of a broad fibrotic gene program, and was required for TGFβ-induced myofibroblast activation. CRISPR interference of the most dynamic cis-element within the enhancer, marked by nascent transcription, prevented TGFβ-induced activation of Meox1. These findings identify MEOX1 as a central regulator of stress-induced myofibroblast activation associated with cardiac dysfunction. The plasticity and specificity of the BET-dependent regulation of MEOX1 in endogenous tissue fibroblasts provides new trans- and cis- targets for treating fibrotic disease.

Abstract 82: Mnsodtg Mice Exhibit Improved Heart and Mitochondrial Function During Chronic Chagas Disease

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jianjun Wen ◽  
Craig Porter ◽  
David Herndon ◽  
Nisha J Garg
Keyword(s):  
Chagas Disease ◽  
Mitochondrial Function ◽  
Heart Function ◽  
Heart Tissue ◽  
Oxygen Flux ◽  
Wild Type ◽  
Ros Scavenging ◽  
Scavenging Capacity ◽  
The Impact ◽  
Chronic Chagas Disease

Background: We observed that mitochondrial reactive oxygen species (mtROS) plays very important roles in the pregression of chagesic disease (CD). In this study, we utilized genetically-modified mice to scavenge mtROS to investigate the impact of improved ROS scavenging capacity on heart function in CD. Methods and Results: C57BL/6 mice (wild-type, MnSODtg, MnSOD+/-) were infected with Trypanosoma cruzi(Tc). Chronically infected mice (≥120dpi) exhibited a substantial decrease in heart tissue MnSOD gene expression, protein level, enzyme activity and antioxidant level; decrease of heart dysfunction via lower of SV, CO, EF, FS and LVPW,s, and increase of ESV/EDS and LVID;s; enhancement of hypertrophy by increase of IVS, LV mass and areas duo to augmentation of collagen expressions. One of our novel observations was that sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) lost its role of maintenance of low cytoplasm free calcium and mediated calcium uptake to intracellular store in Tc-induced chronic chagasic disease. Studies of fresh heart slices using O2K confirmed that Tc diminished heart mitochondrial function like decrease of oxygen flux and respiratory control ratio (RCR), which were caused by enhancements of ROS. Myocardial mitochondrial damage was pronounced and associated with a >x% decline in mitochondrial oxygen flux in chronically infected wild-type and MnSOD transgenic mice. Imaging of intact heart for cardiomyocytes and collagen by the nonlinear optical microscopy techniques showed significant increase in collagen (>x0-fold) in chronically infected wild-type mice; while MnSODtg mice exhibited a basal increase in collagen that did not change during chronic phase. Chronically infected MnSODtg mice exhibited a marginal decline in Tc-induced heart function, heart hypertrophy, mitochondrial dysfunction Conclusions: Overexpression of MnSOD inhibited Tc-induced oxidative damage od heart tissue. , suggesting that enhancing the mitochondrial ROS scavenging capacity was beneficial in controlling the inflammatory and oxidative pathology, and cardiac remodeling responses that are hallmarks of chronic Chagas disease.

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